Abstract
Senescence restricts the development of applications involving mesenchymal stem cells (MSCs) in research fields, such as tissue engineering, and stem cell therapeutic strategies. Understanding the mechanisms underlying natural aging processes may contribute to the development of novel approaches to preventing age-related diseases or slowing individual aging processes. Nampt is a rate-limiting NAD biosynthetic enzyme that plays critical roles in energy metabolism, cell senescence and maintaining life spans. However, it remains unknown whether Nampt influences stem cell senescence. In this study, the function of Nampt was investigated using a rat model of natural aging. Our data show that Nampt expression was significantly lower in MSCs obtained from aged rats than in those obtained from young rats during physiological aging. Reducing the level of Nampt in aged MSCs resulted in lower intracellular concentrations of NAD+ and downregulated Sirt1 expression and activity. After the Nampt inhibitor FK866 was added, young MSCs were induced to become aged cells. The enhanced senescence was correlated with NAD+ depletion and Sirt1 activity attenuation. In addition, Nampt overexpression attenuated cell senescence in aged MSCs. Our findings provide a new explanation for the mechanisms underlying stem cell senescence and a novel target for delaying stem cell senescence and preventing and treating age-related diseases.
Highlights
Cell senescence is a key characteristic of individual aging processes [1]
The length and width of the cells were used to measure cell areas, and the results revealed that while the cell areas of the mesenchymal stem cells (MSCs) obtained from old rats progressively increased (Fig 1C), their cell aspect ratios gradually decreased (Fig 1D)
MSCs derived from both 1- to 2-month-old rats and 15- to 18-month-old rats were used to investigate the effects of age on biological characteristics and cellular senescence
Summary
Cell senescence is a key characteristic of individual aging processes [1]. The aging of stem cells has been shown to be the cellular basis underlying many age-related diseases [2], such as Alzheimer’s disease, osteoporosis, and atherosclerosis [3]. Age-related senescence limits the development of applications involving stem cells that can be used in tissue regenerative and cell therapeutic approaches. The regenerative ability of mesenchymal stem cells (MSCs) that are obtained from aged individual is limited, and this severely restricts their therapeutic effects during autologous stem cell transplantation. PLOS ONE | DOI:10.1371/journal.pone.0170930 January 26, 2017
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